Comprehensive assessments and related interventions to enhance the long-term outcomes of child, adolescent and young adult cancer survivors - presentation of the CARE for CAYA-Program study protocol and associated literature review.

BACKGROUND: Improved, multimodal treatment strategies have been shown to increase cure rates in cancer patients. Those who survive cancer as a child, adolescent or young adult (CAYA), are at a higher risk for therapy-, or disease-related, late or long-term effects. The CARE for CAYA-Program has been developed to comprehensively assess any potential future problems, to offer need-based preventative interventions and thus to improve long-term outcomes in this particularly vulnerable population. METHODS: The trial is designed as an adaptive trial with an annual comprehensive assessment followed by needs stratified, modular interventions, currently including physical activity, nutrition and psycho-oncology, all aimed at improving the lifestyle and/or the psychosocial situation of the patients. Patients, aged 15-39 years old, with a prior cancer diagnosis, who have completed tumour therapy and are in follow-up care, and who are tumour free, will be included. At baseline (and subsequently on an annual basis) the current medical and psychosocial situation and lifestyle of the participants will be assessed using a survey compiled of various validated questionnaires (e.g. EORTC QLQ C30, NCCN distress thermometer, PHQ-4, BSA, nutrition protocol) and objective parameters (e.g. BMI, WHR, co-morbidities like hyperlipidaemia, hypertension, diabetes), followed by basic care (psychological and lifestyle consultation). Depending on their needs, CAYAs will be allocated to preventative interventions in the above-mentioned modules over a 12-month period. After 1 year, the assessment will be repeated, and further interventions may be applied as needed. During the initial trial phase, the efficacy of this approach will be compared to standard care (waiting list with intervention in the following year) in a randomized study. During this phase, 530 CAYAs will be included and 320 eligible CAYAs who are willing to participate in the interventions will be randomly allocated to an intervention. Overall, 1500 CAYAs will be included and assessed. The programme is financed by the innovation fund of the German Federal Joint Committee and will be conducted at 14 German sites. Recruitment began in January 2018. DISCUSSION: CAYAs are at high risk for long-term sequelae. Providing structured interventions to improve lifestyle and psychological situation may counteract against these risk factors. The programme serves to establish uniform regular comprehensive assessments and need-based interventions to improve long-term outcome in CAYA survivors. TRIAL REGISTRATION: Registered at the German Clinical Trial Register (ID: DRKS00012504, registration date: 19th January 2018).

Vitamin D and Mammographic Findings.

Introduction: Pleiotropic immune-modulatory and anti-proliferative effects of vitamin D and hopes to stop cancerogenesis have led to an increased interest in possible reduction of breast cancer with higher vitamin D levels. Mammographic density is an established risk factor for breast cancer risk, and its association with serum vitamin D is complex, as recent studies have shown. Patients and Methods: In this cross-sectional study, 1103 participants were recruited in the breast diagnostic unit of the Klinikum rechts der Isar, TU Munich. A standardised questionnaire and blood samples for 25-OH-vitamin D were taken on the day of mammography. Histologic results of biopsies in suspicious mammographies were documented. Results: In the 1090 data-sets analysed, vitamin D-deficiency was common among women under 40. Highest vitamin D values were observed in participants aged 60-69 years, but average values for all age cohorts were below 20 ng/ml of vitamin D. 15.6 % of all participants had very low vitamin D values (< 10 ng/ml), 51.3 % were vitamin D-deficient (10-19 ng/ml) and only 5.7 % were above 30 ng/ml, i.e. showed sufficient vitamin D. Patients with malignant results had vitamin D < 10 ng/ml more often (16.9 %; p = 0.61), and only 3.4 % in this group had sufficient vitamin D supply (> 30 ng/ml). There were no significant differences in vitamin D-levels between density groups according to the American College of Radiology (ACR) criteria. Conclusion: Vitamin D values were lower than in comparable US women. Up to now, there is no direct clinical evidence for a relationship between the risk for breast cancer and a specific vitamin D value.

Search for drug information: technology implications for rural consumers and pharmacies.

As they age, baby boomers represent a larger proportion of the population experiencing health-related problems. As such, they are growing users of prescription medications. With pharmaceutical companies increasing their use of the Internet for direct-to-consumer advertising, and boomers leading in the routine use of technology, a shift in the sources used to obtain drug information may occur. Analyzing data from a panel of rural Illinois residents, this paper examines some aspects of the current dynamics of prescription drug information sources and their consequences for rural consumers and pharmacies.

Consumer and provider evaluation of rural pharmacy services.

This paper compares consumer and provider perceptions regarding access to pharmacy services in rural Illinois, given a decrease in the number of pharmacies. Consumer data are from the Illinois Rural Life Panel in which more than 1,800 respondents answered questions about availability and use of pharmacy services and about insurance coverage and cost. A survey of all licensed retail pharmacies in 74 rural Illinois counties and in seven non-rural counties provided pharmacy background information and was the source of data on changes in profitability and payment sources. The data provided insight on factors that affect access. Descriptive statistics were used to analyze data from both groups to compare perceptions about access. The objective was to evaluate current access to pharmacy services and implications for future access from the perspective of consumers and pharmacists. Results from rural consumers show access is currently good; 77 percent have a local pharmacy, and 64 percent prefer this source. Future access is of more concern. Pharmacy survey results show 81.5 percent of rural pharmacies are experiencing declining profits from drug sales. Restricted reimbursements from third-party payers, demands of managed care and expanded competition are seen as threats to retention of local pharmacies and continued good access. An important finding, especially given survey evidence of increased managed care penetration, is the difference in views of pharmacists and consumers regarding the effects of managed care on access. Pharmacy survey data also revealed differences between rural and non-rural pharmacies.

Restrictive practice environment and nurse practitioners' prescriptive authority.

This study analyzes the impacts of several variables, including a restrictive practice environment, on a nurse practitioner's level of autonomy with respect to prescribing selected categories of medicines. A general linear model is applied to data from the 1992 national sample of nurse practitioners. Results show that among the significant independent variables, a restrictive environment of imposed state laws and regulations reduces nurse practitioners' level of autonomy in prescribing medications and acts as a barrier to their practicing to full potential. Results and policy implications are discussed.

Returns to nursing education: rural and nonrural practice.

This study uses data from a national sample of registered nurses to compare earnings of nurses in rural and nonrural practice. The comparisons, conditioned by the nurses' education level, are analogous to the concept of "returns to human capital investment" used in labor economics. A general linear model is applied within a framework of labor economics analysis. Results show that nurses with more education receive less for their investment if they practice in rural areas. Work experience and employment setting are also related to lower annualized earnings for rural practice. One exception to the otherwise consistent findings is that returns to advanced practice nursing are higher in rural areas. Results and policy implications are discussed.

Clinical database repository--a solution for outcomes assessment.

This paper describes how implementation of a Clinical Database Repository (CDR) presents health care organizations with a tool to respond actively to quality and cost demands of the current delivery setting. The CDR is an innovative technological solution to integrate unlimited laboratory data with data from other systems, thereby expanding the contribution of routinely collected laboratory data to broader outcomes assessment goals of an organization. The technical components of a CDR, implementation methods, and deployment benefits to an organization are discussed. The resulting outcomes assessment from this tool will enable an organization to positively and cost-effectively influence how care is provided through system rules validation, measuring benefits of new technology, reducing unwarranted practice pattern variation, and validating practice guidelines. Although the value of systems such as CDR has been documented, their full potential for outcomes assessment has yet to be explored.

Birth outcomes to rural Illinois residents: is there a crisis?

In recent years, the supply of obstetric services in rural areas has been a concern. At the same time, the demand for such services has been affected by the reduction in population and economic base. This article explores the extent of these trends in Illinois and whether they have led to a deterioration in amount of prenatal care and birth outcomes. Using birth certificate and infant death data for residents of rural Illinois counties in 1983 and 1988, prenatal care and birth outcomes for each year are compared within rural areas and to the rest of the state, as well as between the two time periods. Although rural residents began prenatal care later, they obtained similar qualities of care as their urban counterparts. The data revealed no adverse impact on birth outcomes of residing in increasingly rural areas, nor was there a deterioration during the time period. An attempt was made to identify rural counties that lost providers and/or facilities and those that gained them. Although such a classification scheme is subjective, similar results ensued. While indirect costs such as time and effort to obtain care may have increased, at 1988 levels of care availability there was no crisis in Illinois.

Pulmonary effects of chronic exposure to liposome aerosols in mice.

Administering liposome-encapsulated drugs by aerosols could be a feasible way of targeting drugs to the lung, specifically to pulmonary alveolar macrophages (AM). In the mouse model, we characterized uptake of carboxyfluorescein- (CF-) labeled liposomes by AM in vivo after acute inhalation of liposome aerosols, and the effects of chronic exposure to liposome aerosols on lung histology and AM function. Mice were placed in a nose-only exposure module and exposed to liposome or saline aerosols for 1 h per day, 5 days per week, for 4 weeks. Five mice of both the experimental and control groups were removed weekly and their lungs examined. Liposomes were made from hydrogenated soy phosphatidylcholine (HSPC) at 50 mg/mL. In vivo uptake of liposomes by AM was documented by fluorescence microscopy and flow cytometry of bronchoalveolar lavage (BAL). A consistent amount of 1-3 micrograms of lipid inhaled per dosing per mouse was estimated from fluorescence measurements. Addition of Triton X-100 to BAL caused a significant increase in fluorescence intensity, indicating that liposomes remained intact in the lung for a period of time. The chronic inhalation study showed no histologic changes of the lung or untoward effects on the general health or survival of animals. AM phagocytic function, intracellular killing, and fatty acid composition were not affected. Transmission electron microscopy and morphometry (computerized image analysis) of AM likewise showed no alterations as a result of the treatment. It was concluded that AM uptake of liposomes delivered by aerosol was operant in vivo. This finding validates the concept of alveolar macrophage-directed delivery of liposome-encapsulated agents to the lung via inhalation. It was also concluded that chronic liposome aerosol inhalation in mice produced no untoward effects on survival, histopathology, and macrophage function. These data confirm and extend prior findings regarding the functional and morphologic interactions of liposomes with AM in vitro (Gonzalez-Rothi et al., Exp. Lung Res. 17:687-705, 1991).

Lipophilic N-acylpyrazinamide derivatives: synthesis, physicochemical characterization, liposome incorporation, and in vitro activity against Mycobacterium avium-intracellulare.

N-acetyl-(2), N-caproyl-(3), N-capryl-(4) and N-palmitoyl-pyrazinamide (5) were synthesized by reacting pyrazinamide (1) with acetic anhydride to prepare (2), or by reacting (1) in chloroform with the corresponding acid chlorides to prepare (3-5). Products were identified by high resolution mass spectroscopy, elemental analysis, and 1H NMR. Melting points, enthalpies of fusion, solubility and octanol-water partition coefficients were determined. Hydrolysis of (2) indicated a pseudo first-order, pH-dependent degradation reaction. Apparent half life times of degradation ranged from 74.2 hours at pH 3 to 5.4 hours at pH 7.34. Derivative (5) was incorporated in liposomes consisting of soy phosphatidylcholine and dipalmitoylphosphatidylglycerol (7:3 molar ratio). The in vitro susceptibility of Mycobacterium avium-intracellulare (MAI) to the liposomal compound containing (5) was tested. MAI was susceptible to (5) at concentrations of 12.5-25 micrograms/ml, although MAI is not susceptible to the parent drug (1). Thus, a new class of antimycobacterial agents with physicochemical properties suitable for stable incorporation within liposomes and high antibiotic efficacy against MAI is presented.

Liposomes and pulmonary alveolar macrophages: functional and morphologic interactions.

In vitro toxicity of liposomes and their functional and morphologic interactions with rat pulmonary alveolar macrophage (AMs) were investigated using viability (trypan blue exclusion), phagocytic and killing activity (uptake and digestion of live S. cerevisiae), surface adherence, respiratory burst (nitro-blue tetrazolium reduction), and morphometry (computerized image analysis) as indicators. Liposome stability in physiologic solutions and uptake of liposome-encapsulated carboxyfluorescein (CF) by AMs was assessed by fluorescence spectroscopy and microscopy. Liposomes made from saturated phospholipids and cholesterol were stable, whereas liposomes consisting of unsaturated phospholipids without cholesterol lost 30% to 40% of their content over 24 h. However, CF uptake was highest with unsaturated phospholipid preparations, whereas uptake of the three other formulations was comparable. Although liposome exposure did not affect macrophage viability, a reduction in the number of phagocytizing macrophages to 73% of control was noted after 24-h incubation with the highest lipid concentration tested (10 mumol/ml). Phagocytic killing was similar under all circumstances observed. The fraction of intracellularly killed yeast ranged from 32% to 42% for both control and experimental samples. An increase in cell surface area from 166.1 +/- 39.9 microns 2 on day O (n = 709) to 196.3 +/- 57.6 microns 2 on day 1 (n = 516) and 211.2 +/- 48.0 microns 2 on day 4 (n = 834) was observed after liposome treatment. The corresponding average cell areas of control samples did not change during the observation period. There was no net cell loss of adherence from monolayers as determined by protein assay. The respiratory burst, indicating generation of intracellular superoxide, was also similar--84% to 92% of experimental and control cells under all conditions showed a strong nitro-blue tetrazolium reduction. In summary, in vitro exposure of AMs to large concentrations of liposomes, although producing an increase in macrophage size, was not associated with aberrant macrophage morphologic features, function, or toxicity for the parameters examined.

Financing rural health and medical services.

The provision and utilization of health care services in rural areas are tied directly to the structure of financing. The model of rural health care shaped by federal policies over three decades was significantly altered by changes during the 1980s. With reactions of third-party payers to health care costs rising faster than inflation, the difficulty of accommodating access to care and cost efficiency in provision became evident. This review begins with the literature on patient services and capital financing of rural hospitals, then continues with the financing of clinics, community centers, and other supply forms. Research during the 1980s provides insight into the effects of various financing policies on the supply of services. The demand for health care in rural areas is characterized by less generous third-party coverage, leaving residents paying a larger share of their incomes for care than do urban residents. As a consequence, access to care is especially difficult for low-income and elderly people, heavily dependent upon government financing. Third-party payers have severely reduced cost shifting as a mechanism for taking care of the health care needs of a sizable share of the population, thereby placing providers in an uncomfortable position. Several potential and more formalized financing options for replacing cost shifting are discussed. Several important changes will take place with rural-focused legislation enacted in the late 1980s. These are used to present a rural financing research agenda for the 1990s.

Microtiter plate assay for selecting "macrophage virulent" strains of Mycobacterium avium intracellulare mycobacteria in mouse pulmonary alveolar macrophages.

Currently used macrophage-mycobacterial in vitro infection models require substantial numbers of macrophages. We developed a miniaturized version of such a model, using microtiter plates, which is comparable to standardly published methods, is reproducible, and requires fewer macrophages. In addition to its ease of handling and its economy in time, number of animals, and supplies, this method is preferable when limited numbers of macrophages are available. We have used this assay as a means of selecting human derived isolates from patients with M. avium intracellulare pulmonary disease for their ability to infect and multiply in cultured mouse pulmonary alveolar macrophages.

RCTs: not the answer to the nursing shortage.

An economic analysis was made of the proposal to create registered care technologists (RCTs) as an alternative to nurse market disequilibrium. RCTs may be a short-term solution to some, but more effective options may make use of existing resources.

Preliminary results of total wrist arthroplasty in rheumatoid arthritis using the Trispherical total wrist arthroplasty.

Thirty-two patients underwent 38 arthroplasties for advanced rheumatoid arthritis and marked soft tissue losses. Seven wrists required repair or transfer of at least one tendon for rebalancing. All patients were improved by the implants. Thirty-four of the 38 patients were improved beyond the functional level of a painless wrist arthrodesis. Overall, there were 23 excellent, 10 good, 3 fair, and 2 poor results. The average wrist score was 90.3 points, and the average arc of motion was 38 degrees. There were three cases of migration of the third metacarpal stem and nine cases of lucency about the stems, three of which were progressive or greater than 1 mm. There were no deep infections. There was one reoperation for persistent pain and one for component loosening. There were no cases of implant failure. These results indicate that this total wrist arthroplasty is a safe, reproducible procedure for radiographic class III and IV rheumatoid disease and should be considered a first line of therapy for that group.

Health care financing among the elderly: who really pays the bills?

This paper investigates the issue of who pays the health care bills of the elderly by considering the types of subsidized health insurance protection enjoyed by the noninstitutionalized elderly and the way that increased Medicare cost-sharing efforts in the 1980s are affecting those without additional health insurance subsidies. In making this examination we estimate the out-of-pocket health care expenditures of the elderly either directly or as nonsubsidized medigap premiums by income level, taking into account four types of health insurance subsidies received by elderly persons: Medicare, Medicaid, Veterans Administration health care, and subsidized health insurance from either current or former employers. We find that increased cost sharing is likely to fall most heavily on those elderly least likely to afford it: the poor and near-poor elderly who have only Medicare as a health insurance subsidy, particularly those who are older and sicker and who use Medicare services more heavily. These persons are caught between well-intentioned federal cost-cutting efforts and the often confusing panoply of health insurance programs for the aged, and they will bear an inequitably large portion of any future Medicare cost-sharing initiatives.

A critical analysis of alignment factors influencing functional results following trispherical total wrist arthroplasty.

In a study of the impact of selected patient factors and alignment variables on functional results of total wrist arthroplasty, functional score and range of motion were found to be improved and incidence of component shift and progressive radiolucent lines decreased by proper positioning of the implant center of rotation and restoration of carpal height. Angulation of the implant stems was secondary in importance to the other positioning variables with respect to overall function and durability. A neutral alignment range for this implant arthroplasty was proposed. Within this neutral range, functional score averaged 94 points and range of motion averaged 68 degrees. There were no reoperations, component shifting, or progressive radiolucent lines, and all wrists rated an excellent score.

Long-term results of dorsal stabilization in the rheumatoid wrist.

Dorsal stabilization was performed on 85 rheumatoid wrist in 62 patients for an average follow-up of 6.8 years. Of these, 37 wrists were followed an average of 10 years. The chief component was pain in 79 of the wrists. Pain, on a scale of 0 to 100, showed a preoperative score of 32 and postoperative ratings of 89 for the total group and 96 for the long-term group. Range of motion decreased in virtually all patients. Spontaneous ankylosis occurred in eight wrists. Because of the presence of associated deformities, usually subluxated metacarpophalangeal joints, evaluation of functional improvement of the wrist was difficult. Those hands in which metacarpophalangeal subluxations were corrected or prevented showed maximum functional improvements. The procedure is beneficial for long-term relief of pain and maintenance of a range of motion which arthrodesis would eliminate.

Madelung's deformity. An end-result study of surgical treatment.

A long-term follow-up (average, eight years) of surgical treatment of thirteen cases of Madelung's deformity in eight patients showed that the Darrach procedure was successful when there was mild deformity and that biplane osteotomy of the radius combined with the Darrach procedure was needed for severe deformity. Subluxation of the lunate bone ulnarward occurred after the Darrach procedure but was not clinically symptomatic.